The goal for this project is to better understand the molecular biological changes that occur in the inner ear as a result of endolymphatic hydrops. Endolymphatic hydrops is a condition known to accompany Meniere's disease, a common disorder affecting millions of Americans. Meniere's disease causes both hearing loss and vertigo. Although vertigo has been shown to be controlled via numerous medical and surgical interventions, the hearing loss and subsequent deafness have no known treatment. This is in part due to the lack of knowledge regarding the exact mechanism of hearing loss in Meniere's related endolymphatic hydrops. Better understanding of the mechanisms of hydrops related hearing loss will be important in guiding the development of therapies to prevent such hearing loss. Glutamate and other excitatory amino acid (EAA) receptors are present in the mammalian inner ear and are thought to play a key role in normal hearing but are also implicated in excitotoxic injury when EAA levels are elevated. Neuronal findings have been described in the cochleas of patients with Meniere's disease and animal models of endolymphatic hydrops and these findings suggest that EAA toxicity may be playing an important role in the mediation of associated inner ear injury and subsequent hearing loss. The specific goals of the project include studies of a well-known model of surgically induced endolymphatic hydrops in the guinea pig. Once endolymphatic hydrops has been established, inner ear tissue samples will be collected and subjected to molecular biological techniques that allow for determination of whether messenger RNA levels of genes critical to EAA physiology .are up-regulated or down-regulated. This will provide clues to better understand the exact biochemical pathways that are activated in this condition and possibly provide new treatment strategies to be developed. It is expected that this project will lead to a larger grant in the future that explores and defines the entire cascade of biochemical changes accompanying Meniere's related endolymphatic hydrops and could someday provide better treatment alternatives to patients with Meniere's related hearing loss. [unreadable] [unreadable]